FOXN3: A Forkhead Box Transcription Factor with Roles in Development and Cancer
Comprehensive genomic and functional overview of FOXN3 (CHES1), a tumor suppressor and developmental regulator.
Gene Information Card
| Symbol | FOXN3 |
|---|---|
| Full Name | Forkhead Box N3 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q31.3 |
| NCBI Gene ID | 22921 ncbi.nlm.nih.gov/gene/22921 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | O60516 |
| OMIM ID | 602955 |
| HGNC ID | 12762 |
| Aliases | CHES1, FOXN3L, MGC138290 |
Description
FOXN3 (Forkhead Box N3), also known as CHES1, is a member of the forkhead box (FOX) family of transcription factors. It acts as a transcriptional repressor involved in cell cycle regulation, DNA damage response, and developmental processes. FOXN3 is considered a tumor suppressor, with loss or downregulation observed in several cancers. It localizes to the nucleus and binds DNA via a forkhead domain.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Downregulation of FOXN3 promotes proliferation and metastasis | PMID: 25944712 |
| Colorectal cancer | FOXN3 suppresses Wnt/β-catenin signaling; loss leads to tumor progression | PMID: 28263393 |
| Hepatocellular carcinoma | FOXN3 inhibits cell growth and invasion; reduced expression correlates with poor prognosis | PMID: 29323341 |
| Lung cancer | FOXN3 acts as a tumor suppressor; epigenetic silencing observed | PMID: 25636800 |
| Ovarian cancer | FOXN3 overexpression reduces cell viability and migration | PMID: 27121332 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.2 | Low |
| Heart | 6.5 | Low |
| Kidney | 7.1 | Low |
| Liver | 5.3 | Low |
| Lung | 6.8 | Low |
| Pancreas | 4.9 | Low |
| Spleen | 5.6 | Low |
| Testis | 9.4 | Low |
| Thyroid | 7.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.2 | Embryonic kidney |
| HeLa | 8.5 | Cervical carcinoma |
| MCF7 | 6.3 | Breast cancer |
| A549 | 7.1 | Lung carcinoma |
| HepG2 | 5.8 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1072C>T (p.Arg358*) | Nonsense | Rare | Loss of function; truncated protein |
| c.1450G>A (p.Gly484Arg) | Missense | Rare | Unknown; likely damaging |
| c.1687_1688insA (p.Thr563Asnfs*12) | Frameshift | Rare | Loss of function |
| c.1972C>T (p.Arg658Trp) | Missense | Rare | Unknown; possibly benign |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg358*, p.Thr563Asnfs*12) lead to truncated or absent protein, consistent with tumor suppressor role.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in FOXN3.
Dominant Negative (DN)
No evidence of dominant-negative mutations in FOXN3.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003700 - DNA-binding transcription factor activity | • GO:0000978 - RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • GO:0005634 - nucleus | • GO:0006357 - regulation of transcription by RNA polymerase II |
| • GO:0006974 - cellular response to DNA damage stimulus | • GO:0007049 - cell cycle |
| • GO:0045892 - negative regulation of transcription | • DNA-templated |
| • GO:0008285 - negative regulation of cell population proliferation |
Pathways
• Cell cycle - G1/S transition (negative regulation)
• DNA damage response (p53-independent)
• Wnt signaling pathway (negative regulation via β-catenin)
Protein Summary
FOXN3 is a 658-amino acid protein containing a forkhead DNA-binding domain. It functions as a transcriptional repressor, regulating genes involved in cell cycle arrest and apoptosis. The protein shuttles between nucleus and cytoplasm, but predominantly localizes to the nucleus. Post-translational modifications include phosphorylation. FOXN3 interacts with proteins such as HDAC1 and SIN3A to mediate repression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FOXN3 Knockout HEK293 Cell Line | EDJ-KQ1496 | Human | 1112 | Details Get a Quote |
| FOXN3 Knockout A-549 Cell Line | EDC07558 | Human | 1112 | Details Get a Quote |
| FOXN3 Knockout HCT 116 Cell Line | EDJ-KQ22412 | Human | 1112 | Details Get a Quote |
| FOXN3 Knockout HeLa Cell Line | EDJ-KQ22413 | Human | 1112 | Details Get a Quote |
| FOXN3 Knockout Hep-G2 Cell Line | EDC07559 | Human | 1112 | Details Get a Quote |
| FOXN3（p.S83A and p.S85A） Point Mutation in Hep-G2 Cell Line | EDC03235 | Human | 1112 | Details Get a Quote |
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